Vimaleswaran et al. Nutrition & Metabolism (2015) 12:7 DOI 10.1186/s12986-015-0002-9
BRIEF COMMUNICATION
Open Access
The APOB insertion/deletion polymorphism (rs17240441) influences postprandial lipaemia in healthy adults Karani Santhanakrishnan Vimaleswaran1,2*, Anne M Minihane1,3, Yue Li1,2, Rosalyn Gill4, Julie A Lovegrove1,2, Christine M Williams2 and Kim G Jackson1,2
Abstract Background: Apolipoprotein (apo)B is the structural apoprotein of intestinally- and liver- derived lipoproteins and plays an important role in the transport of triacylglycerol (TAG) and cholesterol. Previous studies have examined the association between the APOB insertion/deletion (ins/del) polymorphism (rs17240441) and postprandial lipaemia in response to a single meal; however the findings have been inconsistent with studies often underpowered to detect genotype-lipaemia associations, focused mainly on men, or with limited postprandial characterisation of participants. In the present study, using a novel sequential test meal protocol which more closely mimics habitual eating patterns, we investigated the impact of APOB ins/del polymorphism on postprandial TAG, non-esterified fatty acids, glucose and insulin levels in healthy adults. Findings: Healthy participants (n = 147) consumed a standard test breakfast (0 min; 49 g fat) and lunch (330 min; 29 g fat), with blood samples collected before (fasting) and on 11 subsequent occasions until 480 min after the test breakfast. The ins/ins homozygotes had higher fasting total cholesterol, LDL-cholesterol, TAG, insulin and HOMA-IR and lower HDL-cholesterol than del/del homozygotes (P < 0.017). A higher area under the time response curve (AUC) was evident for the postprandial TAG (P < 0.001) and insulin (P = 0.032) responses in the ins/ins homozygotes relative to the del/del homozygotes, where the genotype explained 35% and 7% of the variation in the TAG and insulin AUCs, respectively. Conclusions: In summary, our findings indicate that the APOB ins/del polymorphism is likely to be an important genetic determinant of the large inter-individual variability in the postprandial TAG and insulin responses to dietary fat intake. Keywords: APOB gene, Signal peptide polymorphism, Insertion/deletion polymorphism, Postprandial study, Sequential test meals, Triacylglycerol
Findings Introduction
Apolipoprotein (Apo)B is the structural apoprotein of intestinally- (e.g. chylomicrons, apoB-48) and liver- (e.g. very low density lipoprotein (VLDL), apoB-100) derived lipoproteins and plays an important role in the transport of triacylglycerol (TAG) and cholesterol [1]. The APOB insertion/ * Correspondence: [email protected] 1 Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, University of Reading, Reading RG6 6AP, UK 2 Institute for Cardiovascular and Metabolic Research (ICMR), University of Reading, Reading, UK Full list of author information is available at the end of the article
deletion (ins/del) polymorphism (rs17240441), which produces a difference of three amino acids in the signal peptide, has been associated with fasting total cholesterol (TC) [2,3], TAG [4,5], high density lipoprotein-cholesterol (HDL-C) [2] and low density lipoprotein-cholesterol (LDL-C) [2,3] concentrations, along with cardiovascular diseaserelated outcomes [6-11]. In addition, the effect of this polymorphism on lipid metabolism appears to be modulated by dietary fat and cholesterol intakes [4,12]. Non-fasting (postprandial) TAG is now recognised as a highly significant and arguably independent risk factor for cardiovascular disease [13-16]. However, the postprandial
© 2015 Vimaleswaran et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Vimaleswaran et al. Nutrition & Metabolism (2015) 12:7
Page 2 of 6
lipaemic response is highly heterogeneous, with interindividual variability in response to meal ingestion shown to be modulated by environmental and genetic factors [13,14,17]. Previous studies have examined the association between the APOB ins/del polymorphism and postprandial lipaemia in response to a single meal [8,9,18,19] but findings have been inconsistent with studies often underpowered to examine genotype-lipaemia associations, focussed mainly on men, or with limited (both in terms of time-points and measurements) postprandial characterisation of participants. Hence, in the present study, using a novel sequential test meal protocol which more closely mimics habitual eating patterns, we examined the effect of the APOB ins/del polymorphism on postprandial TAG, non-esterified fatty acids (NEFA), glucose and insulin levels in healthy adults. Methods Study participants
The study was performed using postprandial data from 147 healthy participants who underwent the same sequential test meal protocol and similar inclusion/exclusion criteria, at the University of Reading between 1997 and 2007, as previously described [20]. Briefly, healthy men and women aged 20-70 years, with a body mass index (BMI) between 19-32 kg/m2, fasting TAG levels ≤4 mmol/l and total cholesterol ≤8 mmol/l were recruited (Table 1). The studies were approved by the University of Reading Research Ethics Committee and the West Berkshire Health Authority Ethics Committee, and written informed consent was obtained from all participants.
Table 1 Characteristics of the men and women in the postprandial dataset (n = 147) Men
Women
P value
Age (y)
54 ± 10
54 ± 11
0.868
BMI (kg/m2)
27.6 ± 3.1
25.6 ± 3.5
0.002
TC (mmol/l)
6.15 ± 0.94
5.99 ± 0.97
0.390
TAG (mmol/l)
2.05 ± 0.83
1.39 ± 0.50
ins/del > del/del) was only evident in men, a phenomenon we have previously observed in our cohort for the LEPR [20] and APOA5 [22] genotypes. Expression of the biochemical phenotype of this APOB polymorphism has been proposed to be dependent on the population studied [19]. Irrespective of genotype, men had higher BMI, fasting TAG, insulin and HOMA-IR, and lower HDL-C than women (Table 1), which may have influenced the genotype-gender relationships with postprandial TAG handling. However, the small proportion of women in our dataset (n = 35/147) limits definite conclusions that the impact of genotype is only evident in men. Dietary fat quantity has been reported to influence the effect of this genotype on TAG levels, with a greater association observed when participants consumed a highfat than low-fat diet. Xu et al. [4] proposed the overall reduction in TRL synthesis during the low-fat diet to be responsible for the loss of the genotype effect on the intracellular handling of apoB. Furthermore, the TRLTAG content, but not particle number (apoB concentration), was different between the ins/del groups during the high-fat diet indicating this polymorphism may also influence TRL composition. The reduced ability of the ins/ins homozygotes to handle dietary TAG after meal ingestion in the present study was associated with a higher fasting HOMA-IR and postprandial insulin AUC. In the absence of any known direct effect of apoB on insulin production or cellular action, it is likely that the higher insulin levels are in response to higher postprandial TAG. The associated loss of insulin sensitivity would likely impact on various stages of TRL metabolism. However, we did not determine apoB in the present study and hence it is difficult to discriminate between the potential contributions of increased TRL production versus impaired TAG clearance (both highly insulin dependent processes), to the higher TAG response in the insertion allele carriers. In summary, our findings indicate the APOB ins/del polymorphism is likely to be an important determinant of the inter-individual variability in the postprandial TAG and insulin responses to dietary fat intake. However, we were unable to replicate these findings due to
Page 5 of 6
the lack of access to another postprandial cohort with data on this polymorphism. Hence, replication is highly warranted and, to determine in particular whether the penetrance of genotype on the TAG response is genderspecific. Further work is required to investigate the impact of the APOB ins/del polymorphism on TRL metabolism, and coronary heart disease risk. Abbreviations ApoB: Apolipoprotein B; HDL-C: High density lipoprotein-cholesterol; HOMA-IR: Homeostasis assessment model of insulin resistance; LDL-C: Low density lipoprotein-cholesterol; NEFA: Non-esterified fatty acids; TAG: Triacylglycerol; TC: Total cholesterol. Competing interests The authors declare that they have no competing interests. Authors’ contributions KSV performed the statistical analysis and drafted the manuscript. YL contributed to the data analysis. CMW, JAL, AMM and KGJ designed the postprandial studies, with RG providing input into the genetic focus of the work. All authors contributed to and approved the final version of the manuscript. Acknowledgements The authors wish to thank Mrs Jan Luff for her help with volunteer recruitment and Professor Philippa Talmud for her help with the genotyping. Funding The baseline data used for the genotyping analysis was derived from postprandial studies supported by grants from the BBSRC (Reference no. D18350), DEFRA, Unilever Research, Roche Vitamins Ltd, the Agri-Food LINK programme, Raffinerie Tirlemontoise (ORAFTI) and Nestlé between 1996 and 2000. Author details 1 Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, University of Reading, Reading RG6 6AP, UK. 2Institute for Cardiovascular and Metabolic Research (ICMR), University of Reading, Reading, UK. 3Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, UK. 4Boston Heart Diagnostics, Framingham, MA 01702, USA. Received: 20 October 2014 Accepted: 3 February 2015
References 1. Brown MS, Goldstein JL. How LDL receptors influence cholesterol and atherosclerosis. Sci Am. 1984;251:58–66. 2. Kallel A, Feki M, Elasmi M, Souissi M, Sanhaji H, Omar S, et al. Apolipoprotein B signal peptide polymorphism: distribution and influence on lipid parameters in Tunisian population. Physiol Res/Academia Scientiarum Bohemoslovaca. 2007;56:411–7. 3. Hubacek JA, Waterworth DM, Poledne R, Pitha J, Skodova Z, Humphries SE, et al. Genetic determination of plasma lipids and insulin in the Czech population. Clin Biochem. 2001;34:113–8. 4. Xu CF, Tikkanen MJ, Huttunen JK, Pietinen P, Butler R, Humphries S, et al. Apolipoprotein B signal peptide insertion/deletion polymorphism is associated with Ag epitopes and involved in the determination of serum triglyceride levels. J Lipid Res. 1990;31:1255–61. 5. Boekholdt SM, Peters RJ, Fountoulaki K, Kastelein JJ, Sijbrands EJ. Molecular variation at the apolipoprotein B gene locus in relation to lipids and cardiovascular disease: a systematic meta-analysis. Hum Genet. 2003;113:417–25. 6. Gardemann A, Ohly D, Fink M, Katz N, Tillmanns H, Hehrlein FW, et al. Association of the insertion/deletion gene polymorphism of the apolipoprotein B signal peptide with myocardial infarction. Atherosclerosis. 1998;141:167–75.
Vimaleswaran et al. Nutrition & Metabolism (2015) 12:7
7.
8.
9.
10.
11.
12.
13.
14. 15. 16.
17.
18.
19.
20.
21.
22.
Page 6 of 6
De Padua Mansur A, Annicchino-Bizzacchi J, Favarato D, Avakian SD, Machado Cesar LA, Franchini Ramires JA. Angiotensin-converting enzyme and apolipoprotein B polymorphisms in coronary artery disease. Am J Cardiol. 2000;85:1089–93. Regis-Bailly A, Fournier B, Steinmetz J, Gueguen R, Siest G, Visvikis S. Apo B signal peptide insertion/deletion polymorphism is involved in postprandial lipoparticles' responses. Atherosclerosis. 1995;118:23–34. Byrne CD, Wareham NJ, Mistry PK, Phillips DI, Martensz ND, Halsall D, et al. The association between free fatty acid concentrations and triglyceride-rich lipoproteins in the post-prandial state is altered by a common deletion polymorphism of the apo B signal peptide. Atherosclerosis. 1996;127:35–42. Hixson JE, McMahan CA, McGill Jr HC, Strong JP. Apo B insertion/deletion polymorphisms are associated with atherosclerosis in young black but not young white males: Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. Arterioscler Thromb. 1992;12:1023–9. Lamia R, Asma O, Slim K, Jihene R, Imen B, Ibtihel BH, et al. Association of four apolipoprotein B polymorphisms with lipid profile and stenosis in Tunisian coronary patients. J Genet. 2012;91:75–9. Boerwinkle E, Brown SA, Rohrbach K, Gotto Jr AM, Patsch W. Role of apolipoprotein E and B gene variation in determining response of lipid, lipoprotein, and apolipoprotein levels to increased dietary cholesterol. Am J Hum Genet. 1991;49:1145–54. Jackson KG, Poppitt SD, Minihane AM. Postprandial lipemia and cardiovascular disease risk: Interrelationships between dietary, physiological and genetic determinants. Atherosclerosis. 2012;220:22–33. Hyson D, Rutledge JC, Berglund L. Postprandial lipemia and cardiovascular disease. Curr Atheroscler Rep. 2003;5:437–44. Perez-Martinez P, Delgado-Lista J, Perez-Jimenez F, Lopez-Miranda J. Update on genetics of postprandial lipemia. Atheroscler Suppl. 2010;11:39–43. Bansal S, Buring JE, Rifai N, Mora S, Sacks FM, Ridker PM. Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women. JAMA. 2007;298:309–16. Lopez-Miranda J, Marin C. Dietary, physiological, and genetic impacts on postprandial lipid metabolism. In: Montmayeur JP, le Coutre J, editors. Fat detection: taste, texture, and post ingestive effects. Boca Raton (FL): Frontiers in Neuroscience; 2010. Syvanne M, Talmud PJ, Humphries SE, Fisher RM, Rosseneu M, Hilden H, et al. Determinants of postprandial lipemia in men with coronary artery disease and low levels of HDL cholesterol. J Lipid Res. 1997;38:1463–72. Halsall DJ, Martensz ND, Luan J, Maison P, Wareham NJ, Hales CN, et al. A common apolipoprotein B signal peptide polymorphism modifies the relation between plasma non-esterified fatty acids and triglyceride concentration in men. Atherosclerosis. 2000;152:9–17. Jackson KG, Delgado-Lista J, Gill R, Lovegrove JA, Williams CM, Lopez-Miranda J, et al. The leptin receptor Gln223Arg polymorphism (rs1137101) mediates the postprandial lipaemic response, but only in males. Atherosclerosis. 2012;225:135–41. Visvikis S, Chan L, Siest G, Drouin P, Boerwinkle E. An insertion deletion polymorphism in the signal peptide of the human apolipoprotein B gene. Hum Genet. 1990;84:373–5. Olano-Martin E, Abraham EC, Gill-Garrison R, Valdes AM, Grimaldi K, Tang F, et al. Influence of apoA-V gene variants on postprandial triglyceride metabolism: impact of gender. J Lipid Res. 2008;49:945–53.
Submit your next manuscript to BioMed Central and take full advantage of: • Convenient online submission • Thorough peer review • No space constraints or color figure charges • Immediate publication on acceptance • Inclusion in PubMed, CAS, Scopus and Google Scholar • Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit
BRIEF COMMUNICATION
Open Access
The APOB insertion/deletion polymorphism (rs17240441) influences postprandial lipaemia in healthy adults Karani Santhanakrishnan Vimaleswaran1,2*, Anne M Minihane1,3, Yue Li1,2, Rosalyn Gill4, Julie A Lovegrove1,2, Christine M Williams2 and Kim G Jackson1,2
Abstract Background: Apolipoprotein (apo)B is the structural apoprotein of intestinally- and liver- derived lipoproteins and plays an important role in the transport of triacylglycerol (TAG) and cholesterol. Previous studies have examined the association between the APOB insertion/deletion (ins/del) polymorphism (rs17240441) and postprandial lipaemia in response to a single meal; however the findings have been inconsistent with studies often underpowered to detect genotype-lipaemia associations, focused mainly on men, or with limited postprandial characterisation of participants. In the present study, using a novel sequential test meal protocol which more closely mimics habitual eating patterns, we investigated the impact of APOB ins/del polymorphism on postprandial TAG, non-esterified fatty acids, glucose and insulin levels in healthy adults. Findings: Healthy participants (n = 147) consumed a standard test breakfast (0 min; 49 g fat) and lunch (330 min; 29 g fat), with blood samples collected before (fasting) and on 11 subsequent occasions until 480 min after the test breakfast. The ins/ins homozygotes had higher fasting total cholesterol, LDL-cholesterol, TAG, insulin and HOMA-IR and lower HDL-cholesterol than del/del homozygotes (P < 0.017). A higher area under the time response curve (AUC) was evident for the postprandial TAG (P < 0.001) and insulin (P = 0.032) responses in the ins/ins homozygotes relative to the del/del homozygotes, where the genotype explained 35% and 7% of the variation in the TAG and insulin AUCs, respectively. Conclusions: In summary, our findings indicate that the APOB ins/del polymorphism is likely to be an important genetic determinant of the large inter-individual variability in the postprandial TAG and insulin responses to dietary fat intake. Keywords: APOB gene, Signal peptide polymorphism, Insertion/deletion polymorphism, Postprandial study, Sequential test meals, Triacylglycerol
Findings Introduction
Apolipoprotein (Apo)B is the structural apoprotein of intestinally- (e.g. chylomicrons, apoB-48) and liver- (e.g. very low density lipoprotein (VLDL), apoB-100) derived lipoproteins and plays an important role in the transport of triacylglycerol (TAG) and cholesterol [1]. The APOB insertion/ * Correspondence: [email protected] 1 Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, University of Reading, Reading RG6 6AP, UK 2 Institute for Cardiovascular and Metabolic Research (ICMR), University of Reading, Reading, UK Full list of author information is available at the end of the article
deletion (ins/del) polymorphism (rs17240441), which produces a difference of three amino acids in the signal peptide, has been associated with fasting total cholesterol (TC) [2,3], TAG [4,5], high density lipoprotein-cholesterol (HDL-C) [2] and low density lipoprotein-cholesterol (LDL-C) [2,3] concentrations, along with cardiovascular diseaserelated outcomes [6-11]. In addition, the effect of this polymorphism on lipid metabolism appears to be modulated by dietary fat and cholesterol intakes [4,12]. Non-fasting (postprandial) TAG is now recognised as a highly significant and arguably independent risk factor for cardiovascular disease [13-16]. However, the postprandial
© 2015 Vimaleswaran et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Vimaleswaran et al. Nutrition & Metabolism (2015) 12:7
Page 2 of 6
lipaemic response is highly heterogeneous, with interindividual variability in response to meal ingestion shown to be modulated by environmental and genetic factors [13,14,17]. Previous studies have examined the association between the APOB ins/del polymorphism and postprandial lipaemia in response to a single meal [8,9,18,19] but findings have been inconsistent with studies often underpowered to examine genotype-lipaemia associations, focussed mainly on men, or with limited (both in terms of time-points and measurements) postprandial characterisation of participants. Hence, in the present study, using a novel sequential test meal protocol which more closely mimics habitual eating patterns, we examined the effect of the APOB ins/del polymorphism on postprandial TAG, non-esterified fatty acids (NEFA), glucose and insulin levels in healthy adults. Methods Study participants
The study was performed using postprandial data from 147 healthy participants who underwent the same sequential test meal protocol and similar inclusion/exclusion criteria, at the University of Reading between 1997 and 2007, as previously described [20]. Briefly, healthy men and women aged 20-70 years, with a body mass index (BMI) between 19-32 kg/m2, fasting TAG levels ≤4 mmol/l and total cholesterol ≤8 mmol/l were recruited (Table 1). The studies were approved by the University of Reading Research Ethics Committee and the West Berkshire Health Authority Ethics Committee, and written informed consent was obtained from all participants.
Table 1 Characteristics of the men and women in the postprandial dataset (n = 147) Men
Women
P value
Age (y)
54 ± 10
54 ± 11
0.868
BMI (kg/m2)
27.6 ± 3.1
25.6 ± 3.5
0.002
TC (mmol/l)
6.15 ± 0.94
5.99 ± 0.97
0.390
TAG (mmol/l)
2.05 ± 0.83
1.39 ± 0.50
ins/del > del/del) was only evident in men, a phenomenon we have previously observed in our cohort for the LEPR [20] and APOA5 [22] genotypes. Expression of the biochemical phenotype of this APOB polymorphism has been proposed to be dependent on the population studied [19]. Irrespective of genotype, men had higher BMI, fasting TAG, insulin and HOMA-IR, and lower HDL-C than women (Table 1), which may have influenced the genotype-gender relationships with postprandial TAG handling. However, the small proportion of women in our dataset (n = 35/147) limits definite conclusions that the impact of genotype is only evident in men. Dietary fat quantity has been reported to influence the effect of this genotype on TAG levels, with a greater association observed when participants consumed a highfat than low-fat diet. Xu et al. [4] proposed the overall reduction in TRL synthesis during the low-fat diet to be responsible for the loss of the genotype effect on the intracellular handling of apoB. Furthermore, the TRLTAG content, but not particle number (apoB concentration), was different between the ins/del groups during the high-fat diet indicating this polymorphism may also influence TRL composition. The reduced ability of the ins/ins homozygotes to handle dietary TAG after meal ingestion in the present study was associated with a higher fasting HOMA-IR and postprandial insulin AUC. In the absence of any known direct effect of apoB on insulin production or cellular action, it is likely that the higher insulin levels are in response to higher postprandial TAG. The associated loss of insulin sensitivity would likely impact on various stages of TRL metabolism. However, we did not determine apoB in the present study and hence it is difficult to discriminate between the potential contributions of increased TRL production versus impaired TAG clearance (both highly insulin dependent processes), to the higher TAG response in the insertion allele carriers. In summary, our findings indicate the APOB ins/del polymorphism is likely to be an important determinant of the inter-individual variability in the postprandial TAG and insulin responses to dietary fat intake. However, we were unable to replicate these findings due to
Page 5 of 6
the lack of access to another postprandial cohort with data on this polymorphism. Hence, replication is highly warranted and, to determine in particular whether the penetrance of genotype on the TAG response is genderspecific. Further work is required to investigate the impact of the APOB ins/del polymorphism on TRL metabolism, and coronary heart disease risk. Abbreviations ApoB: Apolipoprotein B; HDL-C: High density lipoprotein-cholesterol; HOMA-IR: Homeostasis assessment model of insulin resistance; LDL-C: Low density lipoprotein-cholesterol; NEFA: Non-esterified fatty acids; TAG: Triacylglycerol; TC: Total cholesterol. Competing interests The authors declare that they have no competing interests. Authors’ contributions KSV performed the statistical analysis and drafted the manuscript. YL contributed to the data analysis. CMW, JAL, AMM and KGJ designed the postprandial studies, with RG providing input into the genetic focus of the work. All authors contributed to and approved the final version of the manuscript. Acknowledgements The authors wish to thank Mrs Jan Luff for her help with volunteer recruitment and Professor Philippa Talmud for her help with the genotyping. Funding The baseline data used for the genotyping analysis was derived from postprandial studies supported by grants from the BBSRC (Reference no. D18350), DEFRA, Unilever Research, Roche Vitamins Ltd, the Agri-Food LINK programme, Raffinerie Tirlemontoise (ORAFTI) and Nestlé between 1996 and 2000. Author details 1 Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, University of Reading, Reading RG6 6AP, UK. 2Institute for Cardiovascular and Metabolic Research (ICMR), University of Reading, Reading, UK. 3Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, UK. 4Boston Heart Diagnostics, Framingham, MA 01702, USA. Received: 20 October 2014 Accepted: 3 February 2015
References 1. Brown MS, Goldstein JL. How LDL receptors influence cholesterol and atherosclerosis. Sci Am. 1984;251:58–66. 2. Kallel A, Feki M, Elasmi M, Souissi M, Sanhaji H, Omar S, et al. Apolipoprotein B signal peptide polymorphism: distribution and influence on lipid parameters in Tunisian population. Physiol Res/Academia Scientiarum Bohemoslovaca. 2007;56:411–7. 3. Hubacek JA, Waterworth DM, Poledne R, Pitha J, Skodova Z, Humphries SE, et al. Genetic determination of plasma lipids and insulin in the Czech population. Clin Biochem. 2001;34:113–8. 4. Xu CF, Tikkanen MJ, Huttunen JK, Pietinen P, Butler R, Humphries S, et al. Apolipoprotein B signal peptide insertion/deletion polymorphism is associated with Ag epitopes and involved in the determination of serum triglyceride levels. J Lipid Res. 1990;31:1255–61. 5. Boekholdt SM, Peters RJ, Fountoulaki K, Kastelein JJ, Sijbrands EJ. Molecular variation at the apolipoprotein B gene locus in relation to lipids and cardiovascular disease: a systematic meta-analysis. Hum Genet. 2003;113:417–25. 6. Gardemann A, Ohly D, Fink M, Katz N, Tillmanns H, Hehrlein FW, et al. Association of the insertion/deletion gene polymorphism of the apolipoprotein B signal peptide with myocardial infarction. Atherosclerosis. 1998;141:167–75.
Vimaleswaran et al. Nutrition & Metabolism (2015) 12:7
7.
8.
9.
10.
11.
12.
13.
14. 15. 16.
17.
18.
19.
20.
21.
22.
Page 6 of 6
De Padua Mansur A, Annicchino-Bizzacchi J, Favarato D, Avakian SD, Machado Cesar LA, Franchini Ramires JA. Angiotensin-converting enzyme and apolipoprotein B polymorphisms in coronary artery disease. Am J Cardiol. 2000;85:1089–93. Regis-Bailly A, Fournier B, Steinmetz J, Gueguen R, Siest G, Visvikis S. Apo B signal peptide insertion/deletion polymorphism is involved in postprandial lipoparticles' responses. Atherosclerosis. 1995;118:23–34. Byrne CD, Wareham NJ, Mistry PK, Phillips DI, Martensz ND, Halsall D, et al. The association between free fatty acid concentrations and triglyceride-rich lipoproteins in the post-prandial state is altered by a common deletion polymorphism of the apo B signal peptide. Atherosclerosis. 1996;127:35–42. Hixson JE, McMahan CA, McGill Jr HC, Strong JP. Apo B insertion/deletion polymorphisms are associated with atherosclerosis in young black but not young white males: Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. Arterioscler Thromb. 1992;12:1023–9. Lamia R, Asma O, Slim K, Jihene R, Imen B, Ibtihel BH, et al. Association of four apolipoprotein B polymorphisms with lipid profile and stenosis in Tunisian coronary patients. J Genet. 2012;91:75–9. Boerwinkle E, Brown SA, Rohrbach K, Gotto Jr AM, Patsch W. Role of apolipoprotein E and B gene variation in determining response of lipid, lipoprotein, and apolipoprotein levels to increased dietary cholesterol. Am J Hum Genet. 1991;49:1145–54. Jackson KG, Poppitt SD, Minihane AM. Postprandial lipemia and cardiovascular disease risk: Interrelationships between dietary, physiological and genetic determinants. Atherosclerosis. 2012;220:22–33. Hyson D, Rutledge JC, Berglund L. Postprandial lipemia and cardiovascular disease. Curr Atheroscler Rep. 2003;5:437–44. Perez-Martinez P, Delgado-Lista J, Perez-Jimenez F, Lopez-Miranda J. Update on genetics of postprandial lipemia. Atheroscler Suppl. 2010;11:39–43. Bansal S, Buring JE, Rifai N, Mora S, Sacks FM, Ridker PM. Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women. JAMA. 2007;298:309–16. Lopez-Miranda J, Marin C. Dietary, physiological, and genetic impacts on postprandial lipid metabolism. In: Montmayeur JP, le Coutre J, editors. Fat detection: taste, texture, and post ingestive effects. Boca Raton (FL): Frontiers in Neuroscience; 2010. Syvanne M, Talmud PJ, Humphries SE, Fisher RM, Rosseneu M, Hilden H, et al. Determinants of postprandial lipemia in men with coronary artery disease and low levels of HDL cholesterol. J Lipid Res. 1997;38:1463–72. Halsall DJ, Martensz ND, Luan J, Maison P, Wareham NJ, Hales CN, et al. A common apolipoprotein B signal peptide polymorphism modifies the relation between plasma non-esterified fatty acids and triglyceride concentration in men. Atherosclerosis. 2000;152:9–17. Jackson KG, Delgado-Lista J, Gill R, Lovegrove JA, Williams CM, Lopez-Miranda J, et al. The leptin receptor Gln223Arg polymorphism (rs1137101) mediates the postprandial lipaemic response, but only in males. Atherosclerosis. 2012;225:135–41. Visvikis S, Chan L, Siest G, Drouin P, Boerwinkle E. An insertion deletion polymorphism in the signal peptide of the human apolipoprotein B gene. Hum Genet. 1990;84:373–5. Olano-Martin E, Abraham EC, Gill-Garrison R, Valdes AM, Grimaldi K, Tang F, et al. Influence of apoA-V gene variants on postprandial triglyceride metabolism: impact of gender. J Lipid Res. 2008;49:945–53.
Submit your next manuscript to BioMed Central and take full advantage of: • Convenient online submission • Thorough peer review • No space constraints or color figure charges • Immediate publication on acceptance • Inclusion in PubMed, CAS, Scopus and Google Scholar • Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit
